Continuous Infusion of Norepinephrine vs Phenylephrine During Spinal Anesthesia for Cesarean Section (INPEACE)

NCT06248593 | Recruiting Phase 4

• 1 other identifier: EC01/2024
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to compare norepinephrine and ephedrine in maintaining blood pressure during spinal anaesthesia for elective cesarean delivery. The main questions it aims to answer are:

• Do phenylephrine and norepinephrine administered as manually controlled continuous infusion during elective cesarean delivery have different effects on neonatal outcome ?
• Do phenylephrine and norepinephrine administered as manually controlled continuous infusion during elective cesarean delivery have different effects on maternal hemodynamics? Participants will receive either phenylephrine or norepinephrine infusion, at the time of performing spinal anesthesia, the infusion rate will be adjusted manually depending on maternal arterial pressure.

Conditions

Cesarean Section Complications; Hypotension

Keywords

hypotension; norepinephrine; cesarean delivery; Obstetric anesthesia; Spinal anesthesia; Phenylephrine

Outcome Measures

Primary Outcomes (1)

• Umbilical artery pH

  Umbilical arterial blood (UA) will be sampled from a double-clamped segment of umbilical cord by using arterial blood gas syringes.Umbilical blood gas will be analyzed with a bedside Blood gas Analyzer System.

  Immediately after delivery

Secondary Outcomes (20)

• Umbilical artery base excess

  Immediately after delivery

• Umbilical artery partial pressure of oxygen

  Immediately after delivery

• Umbilical artery partial pressure of carbon dioxide

  Immediately after delivery

• APGAR score

  1 min after delivery

• APGAR score

  5 min after delivery

Study Arms (2)

Phenylephrine

ACTIVE COMPARATOR

The infusion will have a concentration of Phenylephrine of 25 μg/mL and will be initiated at a rate of 96 mL/hour (1.6 mL/minute), that correspond to a phenylephrine rate infusion of 40 μg/min, then the infusion rate will be manually adjusted within the range 0-144 mL/h : PHE (0-60 μg/min).

Drug: Continuous infusion of Phenylephrine

Norepinephrine

EXPERIMENTAL

The infusion will have a concentration of Norepinephrine of 4 μg/mL and will be initiated at a rate of 96 mL/hour (1.6 mL/minute), that correspond to norepinephrine rate infusion of 6.4 μg/min, then the infusion rate will be manually adjusted within the range 0-144 mL/h : Norepinephrine (0-9.6 µg/min).

Drug: Continuous infusion of Norepinephrine

Interventions

Continuous infusion of Norepinephrine DRUG

The rate of norepinephrine infusion will be adjusted according to values of systolic blood pressure measured noninvasively and recorded at 1-minute intervals along the intraoperative period, with the objective of maintaining values near baseline.

Norepinephrine

Continuous infusion of Phenylephrine DRUG

The rate of phenylephrine infusion will be adjusted according to values of systolic blood pressure measured noninvasively and recorded at 1-minute intervals along the intraoperative period, with the objective of maintaining values near baseline.

Phenylephrine

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: As the study is about preventing hypotension in cesarean section. Only pregnant women are eligible.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Full-term, singleton, pregnant women, nonlaboring.
• Scheduled for elective cesarean delivery under spinal anesthesia,
• American Society of Anesthesiologists physical status : 1 or 2
• Baseline systolic BP between 90 and 140 mm Hg.

You may not qualify if:

• Known fetal abnormality.
• Preexisting or pregnancy-induced hypertension, cardiovascular, cerebrovascular or kidney disease.
• Contraindication to spinal anesthesia.
• Peripartum hemorrhage.
• Body mass index above 40 kg/m2.

Sponsors & Collaborators

• Hassan II University: lead

Study Sites (2)

University hospital Hassan II

Fes, 30060, Morocco

NOT YET RECRUITING

University hospital Hassan II

Fes, 30060, Morocco

RECRUITING

Related Publications (13)

• Heesen M, Stewart A, Fernando R. Vasopressors for the treatment of maternal hypotension following spinal anaesthesia for elective caesarean section: past, present and future. Anaesthesia. 2015 Mar;70(3):252-7. doi: 10.1111/anae.13007. Epub 2015 Jan 13. No abstract available.

  PMID: 25583307 BACKGROUND

• Doherty DG, Norris S, Madrigal-Estebas L, McEntee G, Traynor O, Hegarty JE, O'Farrelly C. The human liver contains multiple populations of NK cells, T cells, and CD3+CD56+ natural T cells with distinct cytotoxic activities and Th1, Th2, and Th0 cytokine secretion patterns. J Immunol. 1999 Aug 15;163(4):2314-21.

  PMID: 10438977 BACKGROUND

• Hasanin A, Aiyad A, Elsakka A, Kamel A, Fouad R, Osman M, Mokhtar A, Refaat S, Hassabelnaby Y. Leg elevation decreases the incidence of post-spinal hypotension in cesarean section: a randomized controlled trial. BMC Anesthesiol. 2017 Apr 24;17(1):60. doi: 10.1186/s12871-017-0349-8.

  PMID: 28438121 BACKGROUND

• Veeser M, Hofmann T, Roth R, Klohr S, Rossaint R, Heesen M. Vasopressors for the management of hypotension after spinal anesthesia for elective caesarean section. Systematic review and cumulative meta-analysis. Acta Anaesthesiol Scand. 2012 Aug;56(7):810-6. doi: 10.1111/j.1399-6576.2011.02646.x. Epub 2012 Feb 7.

  PMID: 22313496 BACKGROUND

• Stewart A, Fernando R, McDonald S, Hignett R, Jones T, Columb M. The dose-dependent effects of phenylephrine for elective cesarean delivery under spinal anesthesia. Anesth Analg. 2010 Nov;111(5):1230-7. doi: 10.1213/ANE.0b013e3181f2eae1. Epub 2010 Sep 14.

  PMID: 20841418 BACKGROUND

• Ngan Kee WD, Lee SW, Ng FF, Tan PE, Khaw KS. Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery. Anesthesiology. 2015 Apr;122(4):736-45. doi: 10.1097/ALN.0000000000000601.

  PMID: 25635593 BACKGROUND

• Onwochei DN, Ngan Kee WD, Fung L, Downey K, Ye XY, Carvalho JCA. Norepinephrine Intermittent Intravenous Boluses to Prevent Hypotension During Spinal Anesthesia for Cesarean Delivery: A Sequential Allocation Dose-Finding Study. Anesth Analg. 2017 Jul;125(1):212-218. doi: 10.1213/ANE.0000000000001846.

  PMID: 28248702 BACKGROUND

• Vallejo MC, Attaallah AF, Elzamzamy OM, Cifarelli DT, Phelps AL, Hobbs GR, Shapiro RE, Ranganathan P. An open-label randomized controlled clinical trial for comparison of continuous phenylephrine versus norepinephrine infusion in prevention of spinal hypotension during cesarean delivery. Int J Obstet Anesth. 2017 Feb;29:18-25. doi: 10.1016/j.ijoa.2016.08.005. Epub 2016 Aug 28.

  PMID: 27720613 BACKGROUND

• Ngan Kee WD, Lee SWY, Ng FF, Khaw KS. Prophylactic Norepinephrine Infusion for Preventing Hypotension During Spinal Anesthesia for Cesarean Delivery. Anesth Analg. 2018 Jun;126(6):1989-1994. doi: 10.1213/ANE.0000000000002243.

  PMID: 28678073 BACKGROUND

• Belin O, Casteres C, Alouini S, Le Pape M, Dupont A, Boulain T. Manually Controlled, Continuous Infusion of Phenylephrine or Norepinephrine for Maintenance of Blood Pressure and Cardiac Output During Spinal Anesthesia for Cesarean Delivery: A Double-Blinded Randomized Study. Anesth Analg. 2023 Mar 1;136(3):540-550. doi: 10.1213/ANE.0000000000006244. Epub 2022 Oct 24.

  PMID: 36279409 BACKGROUND

• Ngan Kee WD. Phenylephrine infusions for maintaining blood pressure during spinal anesthesia for cesarean delivery: finding the shoe that fits. Anesth Analg. 2014 Mar;118(3):496-8. doi: 10.1213/ANE.0000000000000111. No abstract available.

  PMID: 24557093 BACKGROUND

• Mohta M, Dubey M, Malhotra RK, Tyagi A. Comparison of the potency of phenylephrine and norepinephrine bolus doses used to treat post-spinal hypotension during elective caesarean section. Int J Obstet Anesth. 2019 May;38:25-31. doi: 10.1016/j.ijoa.2018.12.002. Epub 2018 Dec 13.

  PMID: 30685301 BACKGROUND

• Ngan Kee WD. A Random-allocation Graded Dose-Response Study of Norepinephrine and Phenylephrine for Treating Hypotension during Spinal Anesthesia for Cesarean Delivery. Anesthesiology. 2017 Dec;127(6):934-941. doi: 10.1097/ALN.0000000000001880.

  PMID: 28872480 BACKGROUND

MeSH Terms

Conditions

Hypotension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Mohamed Adnane Berdai, MD-PhD

  University hospital Hassan II, Fes, Morocco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mohamed Adnane Berdai, MD-PhD

CONTACT

+212655260752; adnane.berdai@yahoo.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Before starting the study, a simple randomization sequence for at least 140 codes divided into two equal-sized groups will be generated. One code for each patient will be placed into a sealed, opaque, sequentially numbered envelope by a research assistant, who is not involved in patient management or data collection. A Medical staff member who is not involved in subsequent patient care or assessement either, will open the envelope for each patient shortly before commencement of the cesarean delivery and prepared two identical 50-mL syringes according to the code contained in the envelops, patients will be randomly allocated to receive Phenylephrine or Norepinephrine infusion. All the syringes will be labelled as "study drug", therefore it will be impossible for the anesthesiologists involved in patient care to identify whether it contained norepinephrine or phenylephrine.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical professor

Model Details: It's a randomized, double-blind, two-arm, parallel, non-inferiority, controlled trial, which tha aim is to test the hypothesis that neonatal outcome, as assessed by umbilical artery pH, is at least as good (non-inferior) when prophylactic continuous manually controlled infusion of norepinephrine is used to maintain blood pressure during spinal anaesthesia for elective cesarean delivery compared with the same infusion modalities of phenylephrine with more stable blood pressure and less bradycardia.

Study Record Dates

• First Submitted: January 31, 2024
• First Posted: February 8, 2024
• Study Start: January 29, 2025
• Primary Completion: March 15, 2026
• Study Completion: March 15, 2026
• Last Updated: September 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: the IPD and any additional supporting information will become available, 3 months after publication and will be available for a period of 6 months.
• Access Criteria: Undecided now

Locations

MO (2)